DESCRIPTION: (Applicant's Abstract) This application focuses on a side- by- side comparison between quantitative PCR and immunohistochemistry to determine the most suitable method to measure TS expression and to predict response to fluoropyrimidines (FPs). The ability to assess TS expression and the p53 status in liver metastases from patients with colorectal cancer will determine the clinical relevance of TS and p53 in response to FP-based chemotherapy and survival and will lead to improved therapeutic strategies aimed at more efficient inhibition of TS of wt p53 function. The advantage of this particular project is that it will allow the rapid collection of a sufficient number of patient specimens to correlate TS expression and p53 status with response to intraarterial FdUrd/LV/dexamethasone within a CALGB trial. In addition the applicant will determine the clinical significance of the mutational spectrum of p53 tumor regrowth and cancer death. The application contains the following Specific Aims: 1. Compare two sensitive methodologies for quantitation of intratumoral TS expression: immunohistochemical staining with the monoclonal TS-specific antibody and quantitative measurement of gene expression by PCR in tumor specimens from liver metastases from patients with advanced colorectal cancer. 2. Determine the clinical relevance of intratumoral TS expression and p53 status as combined determinants of tumor responsiveness to FP- based chemotherapies and survival in patients with colorectal cancer in this prospective study. 3. Determine if the mutational spectrum of p53 will predict for tumor regrowth. The p53 status will be assessed by cDNA cycle sequencing prior to chemotherapy.